Estrogen regulation of the estrogen receptor and insulinlike growth factor-I in the rat uterus: a potential coupling between effects of estrogen and IGF-I.

The interrelationship between estrogen and insulin-like growth factor-I (IGF-I) in the regulation of uterine growth was studied in the rat. The levels of the estrogen receptor (ER), ER mRNA, and IGF-I mRNA in rat uterus and liver were monitored. Uterine ER in normal cycling rats was highest in proestrus and diestrus, as was IGF-I mRNA. ER mRNA and plasma estradiol peaked in proestrus. Hepatic ER mRNA and IGF-I mRNA were highest in diestrus, whereas ER was not significantly changed during the estrous cycle. The temporal effects of multiple injections or continuous infusion of 17 beta-estradiol in ovariectomized rats were examined. In the uterus of animals subjected to multiple injections, a 10-fold increase in IGF-I mRNA was seen 24 h after the start of the treatment, whereas rats given continuous infusion of estradiol showed a more than 16-fold increase. In both groups, the increase of IGF-I mRNA was transient although estrogen treatment was continued. To study local hormonal effects, ovariectomized rats were given estradiol in vaginal implants. The uterine IGF-I mRNA level increased two-fold in 3 days. The ER mRNA level increased 1.5-fold and the uterine weights were doubled. The plasma estradiol concentration did not change during the treatment. A separate experiment was carried out to establish whether IGF-I itself exercises estrogen-like effects. Ovariectomized rats were given hrIGF-I in osmotic minipumps for 3 days. The uteri of the treated animals weighted significantly more than did the controls. Quantitation of the level of uterine estrogen receptors revealed a significant decrease.(ABSTRACT TRUNCATED AT 250 WORDS)